Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells

Kislay Roy,1,* Yogesh S Patel,1,* Rupinder K Kanwar,1 Rangam Rajkhowa,2 Xungai Wang,2 Jagat R Kanwar1 1Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Centre for Molecular and Medical Research (C-MMR), School of Medicine (SoM), Faculty of Health, 2Institute for Fro...

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Autores principales: Roy K, Patel YS, Kanwar RK, Rajkhowa R, Wang X, Kanwar JR
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Publicado: Dove Medical Press 2015
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spelling oai:doaj.org-article:29a066359bfe489286166131ef3c13742021-12-02T01:10:24ZBiodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells1178-2013https://doaj.org/article/29a066359bfe489286166131ef3c13742015-12-01T00:00:00Zhttps://www.dovepress.com/biodegradable-eri-silk-nanoparticles-as-a-delivery-vehicle-for-bovine--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Kislay Roy,1,* Yogesh S Patel,1,* Rupinder K Kanwar,1 Rangam Rajkhowa,2 Xungai Wang,2 Jagat R Kanwar1 1Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Centre for Molecular and Medical Research (C-MMR), School of Medicine (SoM), Faculty of Health, 2Institute for Frontier Materials (IFM), Deakin University, Waurn Ponds, VIC, Australia *These authors contributed equally to this work Abstract: This study used the Eri silk nanoparticles (NPs) for delivering apo-bovine lactoferrin (Apo-bLf) (~2% iron saturated) and Fe-bLf (100% iron saturated) in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm) showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR)-positive MDA-MB-231 cells, while transferrin receptor (TfR) and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+) cells when compared to MCF-7 (EGFR-) cells. The expression of a prominent anti-cancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer. Keywords: breast cancer, silk nanoparticles, bovine lactoferrin, epidermal growth factor receptor, apoptosisRoy KPatel YSKanwar RKRajkhowa RWang XKanwar JRDove Medical PressarticleBreast cancerSilk nanoparticlesBovine lactoferrinEpidermal growth factor receptor (EGFR)Apoptosis.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss Issue 1, Pp 25-44 (2015)
institution DOAJ
collection DOAJ
language EN
topic Breast cancer
Silk nanoparticles
Bovine lactoferrin
Epidermal growth factor receptor (EGFR)
Apoptosis.
Medicine (General)
R5-920
spellingShingle Breast cancer
Silk nanoparticles
Bovine lactoferrin
Epidermal growth factor receptor (EGFR)
Apoptosis.
Medicine (General)
R5-920
Roy K
Patel YS
Kanwar RK
Rajkhowa R
Wang X
Kanwar JR
Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells
description Kislay Roy,1,* Yogesh S Patel,1,* Rupinder K Kanwar,1 Rangam Rajkhowa,2 Xungai Wang,2 Jagat R Kanwar1 1Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Centre for Molecular and Medical Research (C-MMR), School of Medicine (SoM), Faculty of Health, 2Institute for Frontier Materials (IFM), Deakin University, Waurn Ponds, VIC, Australia *These authors contributed equally to this work Abstract: This study used the Eri silk nanoparticles (NPs) for delivering apo-bovine lactoferrin (Apo-bLf) (~2% iron saturated) and Fe-bLf (100% iron saturated) in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm) showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR)-positive MDA-MB-231 cells, while transferrin receptor (TfR) and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+) cells when compared to MCF-7 (EGFR-) cells. The expression of a prominent anti-cancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer. Keywords: breast cancer, silk nanoparticles, bovine lactoferrin, epidermal growth factor receptor, apoptosis
format article
author Roy K
Patel YS
Kanwar RK
Rajkhowa R
Wang X
Kanwar JR
author_facet Roy K
Patel YS
Kanwar RK
Rajkhowa R
Wang X
Kanwar JR
author_sort Roy K
title Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells
title_short Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells
title_full Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells
title_fullStr Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells
title_full_unstemmed Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells
title_sort biodegradable eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against mda-mb-231 and mcf-7 breast cancer cells
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/29a066359bfe489286166131ef3c1374
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